Pegasparaginase-induced hepatotoxicity in patients with acute lymphocytic leukemia in the Saudi population: A retrospective cohort study

Acute lymphocytic leukemia (ALL) is a hematologic malignancy commonly treated with pegasparaginase (PEG-ASP). Limited data exist on PEG-ASP-induced hepatotoxicity in the Saudi population; therefore, this study aimed to determine the rate and risk factors of PEG-ASP-induced hepatotoxicity in Saudi pediatric and adult ALL patients. This retrospective cohort study reviewed the records of ALL patients who had been treated with or received at least 1 dose of PEG-ASP between 2014 and 2021. Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Bivariate and multiple logistic regression analyses were used to analyze the relationships between the variables and the risk of PEG-ASP-induced hepatotoxicity. A total of 368 patients were included in the study, with an overall hepatotoxicity rate of 38.8 (95% CI = 33.9-43.8) per 100 patients. Hepatotoxicity was observed in 35.7% (n = 117/328) of pediatric patients and 7.6% (n = 25/328) of adult patients. Risk factors of hepatotoxicity were identified: bilirubin level (odds ratio = 1.324, 95% CI = 1.089-1.610), presence of hyperdiploidy (OR = 1.456, 95% CI = 1.112-1.907), PEG-ASP dose (OR = 1.287, 95% CI = 1.021-1.623), and vincristine administration (OR = 1.398, 95% CI = 1.087-1.798). Additionally, the liver function test levels included alanine aminotransferase (OR = 1.512, 95% CI = 1.198-1.909), aspartate aminotransferase (OR = 1.445, 95% CI = 1.156-1.806), and gamma-glutamyl transferase (OR = 1.367, 95% CI = 1.089-1.716). PEG-ASP-induced hepatotoxicity poses a significant risk to Saudi patients with ALL. Further studies are needed to identify additional risk factors and improve the management of hepatotoxicity in ALL patients receiving PEG-ASP.